Hydrochloric Acid → 2-amino-1-[3-(trifluoromethyl)phenyl]-1,8-naphthyridin-4(1H)-one

HRID 2215000Notes

Reaction equation

HRID 2215000 reaction equation
[C:1]([CH:3]([C:9](=[O:27])[C:10]1[C:11]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=2)=[N:12][CH:13]=[CH:14][CH:15]=1)C(OCC)=O)#[N:2].Cl.[OH-].[Na+]>C(O)(=O)C>[NH2:2][C:1]1[N:16]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=2)[C:11]2[C:10]([C:9](=[O:27])[CH:3]=1)=[CH:15][CH:14]=[CH:13][N:12]=2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 21948193Ethyl 2-cyano-3-oxo-3-(2-{[3-(trifluoromethyl)phenyl]amino}-3-pyridinyl)propanoate

Product 1

HCID 219481772-amino-1-[3-(trifluoromethyl)phenyl]-1,8-naphthyridin-4(1H)-oneYield 55%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Ethyl 2-cyano-3-oxo-3-(2-{[3-(trifluoromethyl)phenyl]amino}-3-pyridinyl)propanoate (2.0 g, 5.3 mmol) was heated to 120° C. in a mixture of conc. HCl (4 mL) and glacial acetic acid (2 mL) for 3 h. The reaction mixture was cooled to room temperature, and neutralized by slow addition of NaOH pellets. The mixture was extracted with CH2Cl2 (3×). The combined organic extracts were washed with saturated aqueous NaHCO3 (10 mL) and brine (10 mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by prep-HPLC (YMC-Pack Pro C18 Column, 150×20 mm I.D.; 30–70% CH3CN in water, 20 min.) to afford 2-Amino-1-[3-(trifluoromethyl)phenyl]-1,8-naphthyridin-4(1H)-one (880 mg, 55%): LCMS RT: 2.03 min, MH+: 306.3.

Workup

  1. extractionThe mixture was extracted with CH2Cl2 (3×)
  2. washThe combined organic extracts were washed with saturated aqueous NaHCO3 (10 mL) and brine (10 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by prep-HPLC (YMC-Pack Pro C18 Column, 150×20 mm I.D.; 30–70% CH3CN in water, 20 min.)

Sources & evidence

ORD record
ord-cf441dad51714ccd914212904c165c8d
Source dataset
uspto-grants-2006_09
Patent number
US07109196B2

Reaction notes

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